Genetic analysis of neurodegenerative diseases in a pathology cohort

NEUROBIOLOGY OF AGING

卷:76

Article

Blauwendraat, Cornelis¹  Pletnikova, Olga²  Geiger, Joshua T.¹  Murphy, Natalie A.³  Abramzon, Yevgeniya^3,4  Rudow, Gay²  Mamais, Adamantios³  Sabir, Marya S.¹  Crain, Barbara²  Ahmed, Sarah³  Rosenthal, Liana S.⁵  Bakker, Catherine C.⁵  Faghri, Faraz^3,6  Chia, Ruth³  Ding, Jinhui³  Dawson, Ted M.^5,7,8,9  Pantelyat, Alexander⁵  Albert, Marilyn S.⁵  Nalls, Mike A.^3,10  Resnick, Susan M.¹¹  Ferrucci, Luigi¹²  Cookson, Mark R.³  Hillis, Argye E.⁵  Troncoso, Juan C.^2,5  Scholz, Sonja W.^1,5 

[1] NINDS, Neurodegenerat Dis Res Unit, NIH, 35 Convent Dr,Room 1A-215, Bethesda, MD 20892 USA

[2] Johns Hopkins Univ, Sch Med, Dept Pathol Neuropathol, Baltimore, MD USA

[3] NIA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA

[4] UCL, Dept Mol Neurosci, London, England

[5] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA

[6] Univ Illinois, Dept Comp Sci, Urbana, IL USA

[7] Johns Hopkins Univ, Solomon H Synder Dept Neurosci, Baltimore, MD USA

[8] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA

[9] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Neuroregenerat Program, Baltimore, MD USA

[10] Data Tecn Int, Glen Echo, MD USA

[11] NIA, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA

[12] NIA, Longitudinal Studies Sect, NIH, Baltimore, MD 21224 USA

关键词: Neurodegeneration;    NeuroChip;    Genotype-phenotype;    Brain bank;   

DOI  :  10.1016/j.neurobiolaging.2018.11.007

来源: Elsevier

【 摘 要 】

Molecular genetic research provides unprecedented opportunities to examine genotype-phenotype correlations underlying complex syndromes. To investigate pathogenic mutations and genotype-phenotype relationships in diverse neurodegenerative conditions, we performed a rare variant analysis of damaging mutations in autopsy-confirmed neurodegenerative cases from the Johns Hopkins Brain Resource Center (n = 1243 patients). We used NeuroChip genotyping and C9orf72 hexanucleotide repeat analysis to rapidly screen our cohort for disease-causing mutations. In total, we identified 42 individuals who carried a pathogenic mutation in LRRK2, GBA, APP, PSEN1, MAPT, GRN, C9orf72, SETX, SPAST, or CSF1R, and we provide a comprehensive description of the diverse clinicopathological features of these well-characterized cases. Our study highlights the utility of high-throughput genetic screening arrays to establish a molecular diagnosis in individuals with complex neurodegenerative syndromes, to broaden disease phenotypes and to provide insights into unexpected disease associations. Published by Elsevier Inc.

【 授权许可】

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